NKRF (NF-κB repressing factor) is a multifunctional nuclear protein that primarily functions as a transcriptional repressor of NF-κB signaling pathways 12. The protein enhances DHX15 ATPase activity by stabilizing its functional conformation and is involved in constitutive silencing of interferon beta and iNOS promoters [UniProt summary from PubMed:12381793]. NKRF contains an XRN2 binding domain that enables direct interaction with the 5'-3' exonuclease XRN2, facilitating precursor ribosomal RNA processing and controlling XRN2's spatial distribution in the nucleolus 3. Mechanistically, NKRF inhibits NF-κB activity through multiple pathways, including binding to negative regulatory elements in target gene promoters and interacting with factors like HuR to decrease mRNA stability of inflammatory genes such as MMP2 and MMP9 1. Disease relevance is significant, as NKRF downregulation contributes to pathological cardiac remodeling post-myocardial infarction 1, while its interaction with nuclear G-actin helps repress epithelial-mesenchymal transition 4. NKRF also modulates Alzheimer's disease and atherosclerosis progression through NF-κB pathway regulation 5. Clinically, NKRF represents a potential therapeutic target for cardiac remodeling, cancer chemoresistance, and inflammatory diseases, with its dysfunction linked to poor prognosis in various pathological conditions.